Ephedra “Black Box” Warning Considered By FDA

FDA is suggesting that a "black box" warning appear on the principal display panel of all ephedrine alkaloid-containing dietary supplements, FDA Commissioner Mark McClellan, MD/PhD, said during a Feb. 28 briefing held in Washington, D.C.

According to a notice slated for publication in the March 5 Federal Register, the warning would appear on the PDP of all ephedra products and state: "WARNING: Contains ephedrine alkaloids. Heart attack, stroke, seizure and death have been reported after consumption of ephedrine alkaloids."

The warning would continue: "Not for pregnant or breast-feeding women or persons under 18. Risk of injury can increase with dose or if used during strenuous exercise or with other products containing stimulants (including caffeine). Do not use with certain medications or if you have certain health conditions. Stop use and contact a doctor if side effects occur."

Additional warning language would appear on an "outer informational panel, riser backing, panel extension, outsert, etc.," the proposed rule notes (see chart: " ¹ Ephedra Supplement Proposed Principal Display Panel Warning').

The warnings strongly resemble those included in FDA's original 1997 proposed rule concerning the sale of ephedrine alkaloid-containing dietary supplements (² (Also see "Ephedra-containing dietary supplement across-the-board label warning suggested by FDA." - Pink Sheet, 9 Jun, 1997.), p. 23).

In fact, the remainder of FDA's regulatory actions currently defer to the 1997 proposal, as the Federal Register notice also states the agency is reopening for 30 days the public comment period concerning the 1997 rulemaking.

According to McClellan, reopening the rule's comment period was "the fastest way to establish an up-to-date public record for [supporting] further regulatory action" and restrictions on the sale of ephedra.

The reason FDA put out a specific proposed warning was "so that we can put industry on notice that these kinds of changes are coming," McClellan said, adding "we are fully committed to getting this done as quickly as possible."

In a press release issued Feb. 28, FDA described the effort as part of its goal to "seek rapid public comment on the new evidence on health risks associated with ephedra...[and] a strong new warning label on any ephedra products."

The release additionally notes FDA is seeking "rapid public comment on whether the currently available evidence and medical literature present a 'significant or unreasonable risk of illness or injury' from dietary supplements containing ephedra."

"The law allows FDA to prohibit the sale of a dietary supplement [only] if it 'presents a significant or unreasonable risk of injury,'" the statement says, adding the legal standard "implies a risk-benefit calculation based on the best available scientific evidence."

"To give us the strongest possible basis for further regulatory action, we are asking for quick comments on whether these dietary supplements present an unreasonable risk of harm, and whether it makes sense for FDA to seek new authority in this area," the release continues.

Speaking at the briefing, McClellan said the agency interprets the Dietary Supplement Health & Education Act "to mean that we do not need absolute, definitive, final, scientific proof in order to take action."

However, "we are also seeking comment...on whether - if the statute is not adequate for action - what legislative changes are needed in order for us to protect the public health," he said.

Asked if he would like to see Congress shift the burden of proof regarding whether supplements are safe and effective from FDA back to industry, HHS Secretary Tommy Thompson said, "I certainly think Congress should take a look at at least giving us the authority to suspend products pending a scientific evaluation."

McClellan noted that while "it may be possible to use ephedra safely, in small doses, for some purposes...in the face of continued serious adverse events following the use of ephedra, there is a problem."

The press briefing was spurred by the release of the FDA-commissioned report from RAND Corp., which found that little evidence exists showing ephedra products aid athletic performance. As a result, FDA announced the same day it had issued over two dozen warning letters to firms making unsubstantiated athletic performance claims for ephedrine-alkaloid containing supplements.